Reference - Detail
| RRC ID | 88087 |
|---|---|
| Author | Shalash R, Solomon DM, Levi-Ferber M, von Chrzanowski H, Atrash MK, Nakar B, Avivi MY, Hauschner H, Swisa A, Meléndez A, Shav-Tal Y, Henis-Korenblit S. |
| Title | HLH-30/TFEB Rewires the Chaperone Network to Promote Proteostasis Upon Perturbations to the Coenzyme A and Iron-Sulfur Cluster Biosynthesis Pathways. |
| Journal | Aging Cell |
| Abstract |
The maintenance of a properly folded proteome is critical for cellular function and organismal health, and its age-dependent collapse is associated with a wide range of diseases. Here, we find that despite the central role of Coenzyme A as a molecular cofactor in hundreds of cellular reactions, inhibition of the first and rate-limiting step in CoA biosynthesis can be beneficial and promote proteostasis. Impairment of the cytosolic iron-sulfur cluster formation pathway, which depends on Coenzyme A, similarly promotes proteostasis and acts in the same pathway. Proteostasis improvement by interference with the Coenzyme A/iron-sulfur cluster biosynthesis pathways is dependent on the conserved HLH-30/TFEB transcription factor. Strikingly, under these conditions, HLH-30 promotes proteostasis by potentiating the expression of select chaperone genes, providing a chaperone-mediated proteostasis shield, rather than by its established role as an autophagy and lysosome biogenesis-promoting factor. This reflects the versatile nature of this conserved transcription factor, which can transcriptionally activate a wide range of protein quality control mechanisms, including chaperones and stress response genes alongside autophagy and lysosome biogenesis genes. These results highlight TFEB as a key proteostasis-promoting transcription factor and underscore it and its upstream regulators as potential therapeutic targets in proteostasis-related diseases. |
| Volume | 24(6) |
| Pages | e70038 |
| Published | 2025-6-1 |
| DOI | 10.1111/acel.70038 |
| PMID | 40304211 |
| PMC | PMC12151917 |
| MeSH | Basic Helix-Loop-Helix Leucine Zipper Transcription Factors* / genetics Basic Helix-Loop-Helix Leucine Zipper Transcription Factors* / metabolism Coenzyme A* / biosynthesis Coenzyme A* / metabolism Humans Iron-Sulfur Proteins* / biosynthesis Iron-Sulfur Proteins* / metabolism Molecular Chaperones* / metabolism Proteostasis* |
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| The most frequently cited source | News |
| Total number of mentions | 1 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| C.elegans | tm8231 tm9231 tm1978 |